Atherosclerosis is a vascular disease characterized by the modification of the walls of blood carrying vessels. This modification can take the form of thickening of the vessel wall, eventually forming what are commonly referred to as “plaques.” The mechanisms corresponding to the formation, progression, stabilization, or rupture of these plaques and their effects on humans has been an area of intense research in intravascular medicine. With the advent of interventional cardiology and percutaneous diagnostic and treatment procedures, the patient with coronary atherosclerotic disease was no longer required to automatically submit to coronary by-pass surgery—an extremely invasive procedure with attendant risks and extended recovery time. Coronary stents were developed to revascularize narrowed (stenosed) vessels and millions of theses devices have been placed in patients worldwide. However, current statistics show that, while patient comfort and quality of life has been improved, treatment of coronary atherosclerotic disease by stenting has not significantly reduced the patient mortality. Patients treated with stents are still dying suddenly of heart attack.
Much more is now known about coronary disease than even a decade ago, but there are still many questions to be answered. From retrospective autopsy studies on heart attack victims, it has been shown (ref Virmani) that there is often a portion of the coronary artery tree that is completely blocked by a thrombosis, or blood clot. The thrombosis is typically in the vicinity of a plaque in the vessel wall. Referred to as the “culprit lesion,” it would be this blockage that would cut off the blood supply to a portion of the heart, resulting in death of heart muscle tissue and possibly death of the individual. Certain plaques contain material which, when it comes into contact with blood, causes thrombogenesis, or clot formation. These plaques seem to have formed a reservoir, or core, of thrombogenic material behind a layer of fibrous tissue (“cap”), analogous to an abscess. Through some process or set of processes, the integrity of the fibrous layer can become compromised, whereby blood can eventually come into contact with the thrombogenic core. This can be a sudden event, where the patient had no prior warning or even symptoms. If one categorizes plaques broadly as stable—where they may still progress slowly and eventually restrict the vessel—and unstable—those that can change their status rapidly, among the key questions is: “How can we tell the difference?”
Historically, the search for atherosclerotic disease has been a search for the narrowing in the opening or “lumen” of the vessel. Angiography is one of the oldest intravascular technologies employed for this purpose. The technique typically employs a catheter, introduced percutaneously into the vasculature, that is used to inject a contrast agent, consisting of a radio opaque dye, into the blood vessels of interest. Using x-rays, a two dimensional live (cine) or still image of the vasculature can be obtained. The vessel lumen is visible wherever the contrast agent is able to flow. From these images, one can determine the size of the lumen and the presence of any narrowing or blockage. The presence of a plaque can sometimes be inferred by a diffuse lumen boundary. Despite being standard of care for many years and forming the basis for most therapy decisions, angiography alone suffers from some limitations. First, vessel narrowing is not necessarily rotationally isotropic. With only a single view angle from which to form the 2-D image, areas of narrowing can be underestimated or missed entirely. To obtain images from multiple viewpoints requires more time and exposure of the patient to contrast and x-rays. The nature of the image as a “lumenogram,” along with limited spatial resolution, make it difficult, if not impossible, to make any statement about the characteristics of the tissue in the vessel wall. For example, it is impossible to distinguish between a fibrotic plaque and one with a necrotic, lipid filled core.
Intravascular ultrasound (IVUS) has emerged, in the last 15 years, as an imaging technology to measure tissue structural characteristics, in particular for blood vessels. IVUS employs a specially designed catheter, with an acoustic transducer at the distal tip, to send and receive ultrasonic signals. So called, “mechanical” IVUS catheters consist of a flexible polymer outer sheath, inside of which is a core that rotates and pulls back through the vessel, generating a series of circumferential scans of the vessel wall. The core typically consists of an RF transmission line, connecting the transducer at the distal tip to drive and receive electronics. A helically wound wire cable is typically used to transmit torque from a rotary motor, through the core to the distal tip, to ensure rotation of the tip with consistent angular velocity. Ultrasonic waves are back scattered by human tissue. The strength of the back scatter is a function of tissue properties, including density. The signal returning from tissue from a rotating IVUS catheter can be represented as a radar plot with a 360 degree view of a section of the vessel and the radial dimension showing the strength of the signal return as a function of distance from the center of the catheter. An advantage of IVUS is that it allows one to obtain an image of the inner walls of the vessel, even through intervening blood. With axial image resolution of 100-200 microns and imaging depth of greater than 5 mm, various structures within the vessel wall can be visualized, including areas of calcification and thickening of the arterial wall. Also, the boundary between the lumen and the vessel intima as well as that between the media and the adventitia can be visualized with accuracy good enough to calculate lumen dimensions and the area of plaques, or “plaque burden.”
Optical coherence tomography (OCT) is an emerging technology that also provides structural information similar to IVUS. OCT depends on the scattering of light by tissue and uses the coherence properties of light, for example, using a Michelson interferometer, to determine the distance at which a scattering event occurred. The technique is similar to IVUS in that a catheter is moved over a guidewire into the blood vessel to a region of interest and then the core of the catheter is pulled back to scan the artery. However, there are several key differences. For example, the OCT signal cannot penetrate blood, requiring that the blood be cleared from the area of the vessel being imaged. A variety of methods have been employed to accomplish this, the most promising and least dangerous to the patient being a non-occlusive flush, using a bolus of saline/contrast mix. This method provides several seconds in which to obtain an image of a vessel segment.
Another class of intravascular analysis systems uses chemical analysis modalities. These approaches generally rely on optical spectral analysis including near infrared (NIR), Raman, and fluorescence spectral analysis.
Near Infrared Spectroscopy (NIR or NIRS) is a technique, again using light in the near infrared region of the spectrum, intended not to image the physical structure of the artery, but the chemical constituents, specifically cholesterol, of the arterial wall. Unlike OCT, NIR can perform such measurement through blood. Operation of a NIR catheter is very similar to that of IVUS with regard to insertion into the patient and pullback and acquisition of data. The result is a two dimensional map of the cholesterol, or lipid, content of the artery.
NIRS utilizes an intravascular optical catheter which, similarly to IVUS, is driven by a pullback and rotation unit that simultaneously rotates the catheter head around its longitudinal axis while withdrawing the catheter head through the region of the blood vessel of interest.
During this pullback operation, the spectral response of the inner vessel walls is acquired in a raster scan operation. This provides a spatially-resolved spectroscopic analysis of the region of interest. The strategy is that by determining the spectroscopic response of blood vessel walls, the chemical constituents of those blood vessel walls can be determined by application of chemometric analysis, for example.
In Raman spectral analysis, the inner walls of the blood vessel are illuminated by a narrow band, such as laser, signal. The Raman spectral response is then detected. This response is generated by the inelastic collisions betweens photons and the chemical constituents in the blood vessel walls. This similarly produces chemical information for the vessel walls.
Hybrid IVUS/optical catheters have been proposed. For example, in U.S. Pat. No. 6,949,072, which in incorporated herein by this reference in its entirety, a “device for vulnerable plaque detection” is disclosed. Specifically, this patent is directed to intravascular probe that includes optical waveguides and ports for the near infrared analysis of the blood vessel walls while simultaneously including an ultrasound transducer in the probe in order to enable IVUS analysis of the blood vessel walls.